Aging is associated with an increase in cardiac hypertrophy, a common prelude to heart failure. The career goal of this application is to provide an additional period of protected, rigorous, training to facilitate the candidate's transition from an instructor to an independent investigator in cardiovascular aging. Dr. Morissette has recently made the transition from a non-tenure track Instructor-in -medicine positon at Harvard Medical School, to an independent investigator by aquiring a tenure-track assistant professor position at West Virginia University School of Medicine. Additionally, after receiving broad research training in cardiac hypertrophy and failure under the mentorship of Dr. Anthony Rosenzweig, Dr. Morissette will aquire more direct research training in the biology of aging, as Dr. Stephen Alway has agreed to assume the role as Dr. Morissette's new mentor. The applicant's long-term scientific goal is to elucidate endogenous counter-regulatory mechanisms controlling hypertrophy and the progression to failure, as one approach to identifying potential therapeutic targets. Myostatin is a conserved negative regulator of skeletal muscle that is a potential clinical target in the prevention of muscle wasting diseases such as age-related sarcopenia. The focus of this proposal is to use myostatin-null mice to examine the biological role of myostatin in cardiac growth, failure, and aging. Understanding endogenous mechanisms that limit cardiac hypertrophy may provide novel targets or approaches for managing cardiac hypertrophy and failure. WVU has committed institutional support and resources to Dr. Morissette, which will enable him to execute the proposed research plan. The scientific committee assembled to provide guidance to Dr. Morissette includes experts on cardiovascular and skeletal muscle aging and clinical heart failure. The career development plan includes formal coursework on the biology of aging, participation in journal clubs, seminars, and conferences. As an independent investigator Dr. Morissette will have the opportunity to mentor and train undergraduate and graduate students, as well as medical and post-doctoral fellows within his laboratory, with the benefit of advice and guidance from an established and sucessful mentor, Dr. Alway.[unreadable] [unreadable] Public Health Relevance:[unreadable] These proposed studies may lead to the elucidation of new therapeutic targets to prevent cardiac hypertrophy and heart failure, which could result in a reduction in cardiac morbidity and mortality in the adult and aging population.[unreadable]